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Gelatin and lipidoid integrate to create gelasomes to enhance siRNA delivery with low toxicity

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Bioactive Materials 2024年第10期40卷 557-570页

作者： Abilash Gangula Dhananjay suresh Agasthya suresh Babu Zhaohui Li Anandhi Upendran Raghuraman Kannan Department of Radiology University of MissouriColumbi1MO65212USA Department of Bioengineering University of MissouriColumbi1MO65212USA Department of Medical Pharmacology and Physiology University of MissouriColumbi1MO65212USA Ellis Fischel cancer center University of MissouriColumbi1MO65212USA

RNAi therapeutics possess the potential to cure many uncurable human *** instance,RNAi therapeutics using liposomes showed remarkable survival benefits in patients with liver ***,the extension of liposomes to deliver RNA to cure other ailments has largely been ***,researchers are focusing on designing and testing different combinations of materials for versatile RNA delivery ***,an efficient and safe RNA delivery platform has not been *** this work,we have developed a new class of RNA-delivery vehicle called“Gelasomes,”using an incongruous combination of gelatin and lipidoid to exploit each material’s unique properties while overcoming their inherent *** low in vivo toxicity of Gelasomes is attributed to the exterior gelatin layers that shield the exposure of cationic lipidoid-siRNA clusters and yet present a biocompatible ***,toxicity studies in mice indicate that repeated administration of Gelasomes(up to 48 mg/kg BW)is well-tolerated with no notable changes in body weight,hematology,or serum ***,the gelatin outer layer efficiently protects siRNA from serum degradation(48 h),preserving its functionality beyond two months of ***,Gelasomes possess dual siRNA conjugation modes,i.e.,electrostatic binding with lipidoid core and covalent attachment to gelatin *** bivalency coupled with lipidoids’high transfection efficiency rendered Gelasomes with remarkably high gene silencing efficiency(>90%)at very low treatment doses in vitro(40μg/mL).In vivo studies further confirmed the high gene silencing ability of Gelasomes in non-small cell lung tumor mouse *** new platform is tunable on all fronts:size,degree of surface coating,and biomolecule *** the lipidoid c14-tail to a c8-tail yielded Gelasomes of reduced *** lipidoids with different carbon lengths are synthesizable,we can develop a library of Gelasomes with d

关键词： doses integrate render

Liposome mediated drug delivery for leukocyte adhesion deficieny I （LAD I）： Targeting the mutated gene ITGB2 and expression of cD18 protein

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Frontiers in Biology 2014年第1期9卷 1-4页

作者： c. Subathra DEVI Kritika KEDARINATH Payal cHOUDHARY Vishakha tyagi Mohanasrinivasan. V School of Biosciences and Technology VIT University Vellore 632014 Tamil Nadu India

Leukocyte adhesion deficiency （LAD） I is a disorder caused due to mutations in a gene （ITGB2） located on chromosome 21 and encodes the β2 subunit of the leukocyte integrin molecules. This leads to defects in the adhesion of leukocytes on endothelial cells which further leads to recurrent microbial infections due to a decrease in the immune response. Base Excision Repair Mechanism （BER） is instrumental in repairing damaged DNA by removing mutated/ damaged bases. We have proposed a hypothesis for the treatment of LAD I by making use of the proteins/enzyme complexes responsible for base excision repair mechanism be introduced into the leukocytes via liposomes. This will target the mutated gene in the leukocytes （mostly neutrophils） and DNA repair will occur. The liposomes can be introduced into the patients via intravenous methods.

关键词： cDI8 β-integrin LAD I liposome BER ITGB2

Mitigating phytotoxicity of tetracycline by metal-free 8-hydroxyquinoline functionalized carbon nitride photocatalyst

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Journal of Environmental Sciences 2023年第3期125卷 37-46页

作者： Toshali Bhoyar Devthade Vidyasagar suresh S.Umare Materials and catalysis Laboratory Department of ChemistryVisvesvaraya National Institute of Technology(VNIT)Nagpur 440010India School of Material Science and Engineering Kyungpook National UniversityDaegu 41566Korea

Photooxidative removal of pharmaceuticals and organic dyes is an effective way to eliminate growing micropollutants. However, photooxidation often results in byproducts as secondary hazardous substances such as phytotoxins. Herein, we found that photooxidation of common antibiotic tetracycline hydrochloride(TcH) over a metal-free 8-hydroxyquinoline(8-HQ) functionalized carbon nitride(cN) photocatalyst significantly reduces the TcH phytotoxic effect. The phytotoxicity test of photocatalytic treated TcH-solution evaluated towards seed growth of cicer arietinum plant model endowed natural root and shoot *** study highlights the conceptual insights in designing of metal-free photocatalyst for environmental remediation.

关键词： carbon nitride 8-Hydroxyquinoline Tetracycline hydrochloride Photocatalyst Phytotoxicity cicer arietinum

Systemic treatment strategies for triple-negative breast cancer

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World Journal of clinical Oncology 2014年第2期5卷 125-133页

作者： Budhi Singh Yadav suresh c Sharma Priyanka chanana Swaty Jhamb Department of Radiotherapy PGIMERChandigarh 160012 India

Triple-negative breast cancer(TNBc) is defined by the lack of immunohistochemical expression of the estrogen and progesterone receptors and human epidermal growth factor receptor 2(EGFR2). Most TNBc has a basal-like molecular phenotype by gene expression profiling and shares clinical and pathological features with hereditary BRcA1 related breast cancers. This review evaluates the activity of available chemotherapy and targeted agents in TNBc. A systematic review of PubM ed and conference databases was carried out to identify randomised clinical trials reporting outcomes in women with TNBc treated with chemotherapy and targeted agents. Our review identified TNBc studies of chemotherapy and targeted agents with different mechanisms of action, including induction of synthetic lethality and inhibition of angiogenesis, growth and survival pathways. TNBc is sensitive to taxanes and anthracyclins. Platinum agents are effective in TNBc patients with BRcA1 mutation, either alone or in combination with poly adenosine diphosphate polymerase 1 inhibitors. combinations of ixabepilone and capecitabine have added to progression-free survival(PFS) without survival benefit in metastatic TNBc. Antiangiogenic agents, tyrosine kinase inhibitors and EGFR inhibitorsin combination with chemotherapy produced only modest gains in PFS and had little impact on survival. TNBc subgroups respond differentially to specific targeted agents. In future, the treatment needs to be tailored for a specific patient, depending on the molecular characteristics of their malignancy. TNBc being a chemosensitive entity, combination with targeted agents have not produced substantial improvements in outcomes. Appropriate patient selection with rationale combinations of targeted agents is needed for success.

关键词： Breast cancer Triple negative Basal like BRcA1 Poly(ADP-ribose)polymerase 1 Targeted therapy chemotherapy

Purinergic contraction of the rat vas deferens in L-NAME-induced hypertension：effect of sildenafil

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Asian Journal of Andrology 2010年第3期12卷 415-421,I0012页

作者： Serap Gur suresh c. Sikka Gillian E. Knight Geoffrey Bumstock Wayne J.G. Hellstrom Department of Urology Tulane University Health Sciences Center New Orleans LA 70112 USA Autonomic Neuroscience centre Royal Free and University College Medical School Rowland Hill Street London NW32PF UK

Hypertension （HTN） is a risk factor for erectile dysfunction, but its effect on vas deferens （VD） contractility and the ejaculatory response has not been delineated. NG-nitro-L-arginine methyl ester （L-NAME）, a nitric oxide synthase inhibitor, was used for induction of nitric oxide （NO）-deficient HTN. Our aim was to evaluate the effects of L-NAME-induced HTN on rat VD contractility and to determine whether sildenafil affects VD contractility. A total of 36 male rats were divided into （1） control, （2）L-NAME-HTN, （3） sildenafil treated L-NAME-HTN groups. Group 2 was treated with L-NAME （40 mg kgI per day） in drinking water for 4 weeks. Group 3 received sildenafil （1.5 mg kg^-1 per day, by oral gavage） concomitantly with L-NAME. The prostatic portion of the VD was subjected to electrical field stimulation （EFS, 1-20 Hz）, and the P2X1 agonist α,β-methylene ATP （α,β meATP, 100 μmol L^-1-1 μmol L-1） and the al-adrenoceptor agonist phenylephrine （Phe, 100 μmol L^-1-1 mmol L^-1） were used to construct concentration-response curves. These experiments were repeated in the presence of P2X receptor antagonist, pyridoxalphosphate-6-azophenyl-2＇,4＇-disulfonic acid （PPADS, 30 μmol L-1）. VD contractions in response to EFS, a,β-meATP and Phe were significantly enhanced by L-NAME. Sildenafil treatment in the L-NAME group improved the contractile response of VD to EFS （20 Hz）. In the presence of PPADS, the enhanced contractile response of VD to EFS and a,β-meATP in hypertensive rats was reversed. In the rat model of chronic NO depletion, the purinergic and adrenergic components and EFS affect VD contractility. The VD contractile response may be mediated more by the purinergic system than the adrenergic system, and sildenafil may alter the ejaculatory response in men with PE.

关键词： hypertensive rat NG-nitro-L-arginine methyl ester purinergic receptors P2X sildenafil vas deferens

Endocrine disruptors and estrogenic effects on male reproductive axis

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Asian Journal of Andrology 2008年第1期10卷 134-145页

作者： suresh c. Sikka Run Wang Department of Urology Tulane University Health Sciences Center New Orleans LA 70112-2699 USA Departments of Urology University of Texas Medical School at Houston and University of Texas MD Anderson Cancer Center Houston TX 77030 USA

Endocrine disruptors （e.g., polychlorinated biphenyls [PcBs], dichlorodiphenyl-trichloroethane [DDT], dioxin, and some pesticides） are estrogen-like and anti-androgenic chemicals in the environment. They mimic natural hormones, inhibit the action of hormones, or alter the normal regulatory function of the endocrine system and have potential hazardous effects on male reproductive axis causing infertility. Although testicular and prostate cancers, abnormal sexual development, undescended testis, chronic inflammation, Sertoli-cell-only pattern, hypospadias, altered pituitary and thyroid gland functions are also observed, the available data are insufficient to deduce worldwide conclusions. The development of intra-cytoplasmic sperm injection （IcSI） is beyond doubt the most important recent breakthrough in the treatment of male infertility, but it does not necessarily treat the cause and may inadvertently pass on adverse genetic consequences. Many well-controlled clinical studies and basic scientific discoveries in the physiology, biochemistry, and molecular and cellular biology of the male reproductive system have helped in the identification of greater numbers of men with male factor problems. Newer tools for the detection of Y-chromosome deletions have further strengthened the hypothesis that the decline in male reproductive health and fertility may be related to the presence of certain toxic chemicals in the environment. Thus the etiology, diagnosis, and treatment of male factor infertility remain a real challenge. clinicians should always attempt to identify the etiology of a possible testicular toxicity, assess the degree of risk to the patient being evaluated for infertility, and initiate a plan to control and prevent exposure to others once an association between occupation/toxicant and infertility has been established.

关键词： endocrine disruptors environmental estogens hypothalamic-pituitary-testicular axis oxidative stress male infertility

Rapid bacteria identification using structured illumination microscopy and machine learning

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Journal of Innovative Optical Health Sciences 2018年第1期11卷 149-158页

作者： Yingchuan He Weize Xu Yao Zhi Rohit tyagi Zhe Hu Gang cao college of Engineering Huazhong Agricultural University Wuhan 430070 P.R.China college of Veterinary Medicine Huazhong Agricultural University Wuhan 430070 P.R.China State Key Laboratory of Agricultural Microbiology Huazhong Agricultural University Wuhan 430070 P.R.China Bio-Medical center Huazhong Agricultural University Wuhan 430070 P.R.China Key Laboratory of Development of Veterinary Diagnostic Products Ministry of Agriculture College of Veterinary Medicine Huazhong Agricultural University Wuhan 430070P.R.China

Traditionally,optical microscopy is used to visualize the morphological features of pathogenic bacteria,of which the features are further used for the detection and ident ification of the ***,due to the resolution limitation of conventional optical microscopy as well as the lack of standard pattern library for bacteria identification,the ffectiveness of this optical microscopy-based method is ***,we reported a pilot study on a combined use of Structured Illumination Microscopy(SIM)with machine learning for rapid bacteria *** applying machine learning to the SIM image datasets from three model bacteria(including Escherichia coli,Mycobacterium smegmatis,and Pseudomonas aeruginosa),we obtained a classifcation accuracy of up to 98%.This study points out a promising possibility for rapid bacterial identification by morphological features.

关键词： Structured ilumination microscopy bacterial classification principal component analysis support vector machine random forest

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心肌局部缺血的预适应(英文)

Acta Pharmacologica Sinica 2002年第10期23卷 3-8页

作者： Priya tyagi,Girish TAYAL Department of Pharmacology Maulana Azad Medical college New Delehi 110002 India Department of Pharmacology Maulana Azad Medical college New Delehi 110002 India

Preconditioning of the myocardium with short episodes of sublethal ischemia will delay the onset of necrosis during a subsequent lethal ischemic insult. Ischemic preconditioning seems to involve a variety of stress signals which include activation of membrane receptors and signaling molecules such as protein kinase c, mitogen-acti-vated protein kinases, opening of ATP-sensitive potassium channel, and expression of many protective proteins. The purpose of this review is to assess the current position in this field and to facilitate future research.

关键词：局部缺血预处理腺苷线粒体一氧化氮心肌

comparative evaluation of semen parameters in pre-and post-Hurricane Katrina human population

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Asian Journal of Andrology 2015年第4期17卷 676-680页

作者： caner Baran Wayne J Hellstrom suresh c Sikka Department of Urology Tulane University School of Medicine New Orleans LA 70112 USA.

A natural disaster leading to accumulation of environmental contaminants may have substantial effects on the male reproductive system. Our aim was to compare and assess semen parameters in a normospermic population residing in the Southern Louisiana, USA area pre- and post-Hurricane Katrina. We retrospectively evaluated semen analyses data （n = 3452） of 1855 patients who attended the Tulane University Andrology/Fertility clinic between 1999 and 2013. The study inclusion criteria were men whose semen analyses showed -〉 1.5 ml volume; _〉15 million ml1 sperm concentration; _〉39 million total sperm count; _〉40% motility; 〉30% morphology, with an abstinence interval of 2-7 days. After the inclusion criteria applied to the population, 367 normospermic patients were included in the study. Descriptive statistics and group-based analyses were performed to interpret the differences between the pre-Katrina （Group 1, 1999-2005） and the post-Katrina （Group 2, 2006-2013） populations. There were significant differences in motility, morphology, number of white blood cell, immature germ cell count, pH and presence of sperm agglutination, but surprisingly there were no significant differences in sperm count between the two populations. This long-term comparative analysis further documents that a major natural disaster with its accompanied environmental issues can influence certain semen oarameters （e.g.. motility and morphology） and, bv extension, fertility potential of the population of such areas.

关键词： environment Hurricane Katrina, New Orleans area normospermic infertile population retrospective semen analYSiS